 |
Journal articles
Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope
Abstract : A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic 'breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing. We here engineer E dimers locked by inter-subunit disulfide bonds, and show by X-ray crystallography and by binding to a panel of human antibodies that these engineered dimers do not expose the FLE, while retaining the EDE exposure. These locked dimers are strong immunogen candidates for a next-generation vaccine.
Cited literature [50 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01540166
Contributor : Giovanna Barba Spaeth Connect in order to contact the contributor
Submitted on : Thursday, June 15, 2017 - 7:12:54 PM
Last modification on : Monday, January 10, 2022 - 11:44:05 AM
Long-term archiving on: : Wednesday, December 13, 2017 - 12:09:50 PM
Contributor : Giovanna Barba Spaeth Connect in order to contact the contributor
Submitted on : Thursday, June 15, 2017 - 7:12:54 PM
Last modification on : Monday, January 10, 2022 - 11:44:05 AM
Long-term archiving on: : Wednesday, December 13, 2017 - 12:09:50 PM
File
ncomms15411.pdf
Publication funded by an institution
Licence
Distributed under a Creative Commons Attribution 4.0 International License